Adoptive Autologous iNKT Cells for the Treatment of Progressed Hepatocellular Carcinoma Continuing on PD-1 Inhibitor Therapy

January 12, 2024 updated by: LU JUN, Beijing YouAn Hospital

An Open Label, Randomized, Controlled, Clinical Trial of Adoptive Autologous Invariant Natural Killer T Cells for the Treatment of Progressed Hepatocellular Carcinoma Continuing on PD-1 Inhibitor Therapy

The goal of this clinical trial is to explore the efficacy and safety of autologous iNKT cells in patients with progressed hepatocellular carcinoma (HCC) after treatment with PD-1 antibody. The main question it aims to answer are:

  • the efficacy of autologous iNKT cells in patients with progressed HCC after treatment with PD-1 antibody.
  • the safety of autologous iNKT cells in patients with progressed HCC after treatment with PD-1 antibody.

Participants will be randomized 1:1 to receive Regorafenib + PD-1 + iNKT cells (RPI group) or the treatment of Regorafenib + PD-1 (RP group).

Researchers will compare RPI group and RP group to see whether the iNKT cells can achieve a better therapeutic effect on HCC patients with PD-1 resistance.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Single center, randomized, open trial in Barcelona Clinic Liver Cancer（BCLC）C stage patients with progressed HCC after anti-angiogenic targeted drugs combined with PD-1 monoclonal antibody therapy to explore the efficacy and safety of autologous iNKT cells.

This study includes screening period, treatment period and follow-up period (until the subjects withdrew their informed consent or received other anti-tumor therapy or participated in other clinical trials or the researchers judged that it is not in the best interests of patients to continue to participate in the study) after treatment.

The patients will be randomized 1:1 using a random number table to receive Regorafenib + PD-1 + iNKT cells (RPI group) or the treatment of Regorafenib + PD-1 (RP group).

  1. iNKT Cells：Intravenous infusion. The cells will be infused every two weeks as a course of treatment for up to six courses.
  2. PD-1：Intravenous infusion, according to the drug instructions.
  3. Regorafenib：Oral administration, according to the drug instructions. All target and non-target lesions will be assessed by chest, abdomen, and pelvis CT or MRI at baseline and every 8 weeks until radiological progression (according to mRECIST/iRECIST).

Safety and side-effect profiles will be assessed based on the nature, frequency, and severity of adverse events, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Study Type

Interventional

Enrollment (Estimated)

84

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100069
        • Recruiting
        • Beijing Youan Hospital,Capital Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18-75 years of age.
  • Barcelona Clinic Liver Cancer（BCLC） C stage hepatocellular carcinoma (HCC) confirmed by CT, MRI, and/or histopathology.
  • Progressed after receiving anti-angiogenic targeted drugs combined with PD-1 monoclonal antibody.
  • Life expectancy of at least 12 weeks.
  • Child-Pugh A/B.
  • Voluntary signing of informed consent.

Exclusion Criteria:

  • History of severe hypertension or cardiac disease.
  • known central nervous system (CNS) tumor or combined with other malignant disorders.
  • Uncontrolled immune system or infectious disease.
  • Known history of the human immunodeficiency virus (HIV) or syphilis infection.
  • History of stem cell transplant or organ allograft.
  • History of allergy to immunotherapy or related drugs.
  • Bilirubin is twice times the upper limit of normal.
  • Glomerular filtration rate （GFR）< 60ml/min.
  • Serious complications include moderate or severe infective pleural and peritoneal effusion, pericardial effusion, upper gastrointestinal bleeding, hepatic encephalopathy.
  • Pregnancy or lactation.
  • History of severe allergy to any monoclonal antibody or anti-angiogenic targeted drug.
  • Deemed not suitable for cellular immunotherapy by the investigators.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RPI group
Regorafenib + PD-1 + iNKT cells
Biological: iNKT Cells
the iNKT cells will be intravenous infused every two weeks as a course of treatment for up to six courses , the reinfusion dose is determined according to the patient's body surface area, which was about 108~109cells/m2.
Other Names:
  • Vα24+ T Cells
Drug: PD-1
Intravenous infusion, according to the drug instructions.
Drug: Regorafenib
Oral administration, according to the drug instructions.
Other: RP group
Regorafenib + PD-1
Drug: PD-1
Intravenous infusion, according to the drug instructions.
Drug: Regorafenib
Oral administration, according to the drug instructions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: The time from enrollment to disease progression, or death from any cause, whichever occurred first, up to 24 months.
The time from enrollment to disease progression according to the modified RECIST (mRECIST) guideline in trial immunotherapeutics, or death from any cause, whichever occurred first；the time from enrollment to confirmed disease progression (iCPD) according to the iRECIST
The time from enrollment to disease progression, or death from any cause, whichever occurred first, up to 24 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate (DCR)
Time Frame: Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.
including complete response (CR), partial response (PR), and disease stabilization (SD), evaluated by imaging according to iRECIST for target lesions and assessed by MRI/CT.
Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.
Objective response rate (ORR)
Time Frame: Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.
complete response (CR) and partial response (PR) evaluated by imaging according to mRECIST/iRECIST for target lesions and assessed by MRI/CT.
Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.
Overall survival (OS)
Time Frame: Time from the date of enrollment to the date of death from any cause, up to 36 months.
Time from the date of enrollment to the date of death from any cause.
Time from the date of enrollment to the date of death from any cause, up to 36 months.
1-year overall survival rate (1-year OS rate)
Time Frame: Time from the date of enrollment to 1 year later.
The proportion of subjects who were still alive from the date of enrollment to 1 year later
Time from the date of enrollment to 1 year later.
Duration of Overall Response (DOR)
Time Frame: Time from the first tumor remission to the first recording of disease progression or death from any cause, up to 24 months..
The time from the first tumor remission (CR or PR according to mRECIST/iRECIST) to the first recording of disease progression (PD according to mRECIST criteria or iCPD according to iRECIST) or death from any cause (whichever occurs first).
Time from the first tumor remission to the first recording of disease progression or death from any cause, up to 24 months..
Time to progression (TTP)
Time Frame: Time from the date of enrollment to the date of first disease progression, up to 24 months.
Time from the date of enrollment to the date of first disease progression (PD) according to mRECIST or iCPD according to iRECIST).
Time from the date of enrollment to the date of first disease progression, up to 24 months.
Time to Quality of Life (QoL) Deterioration
Time Frame: Time from the date of enrollment, up to 24 months.

EORTC QLQ-C30: European Organization for Research on Treatment of Cancer Quality of Life Questionnare-Core 30.

The totally 30 items spread out over five functional scales (15 items), three symptom scales (7 items), a global health status/QoL scale (2 items), and six single items. 1-28 item ranges 1: not at all, 2: a little, 3: quite a lit, 4: very much; 29-30 item ranges 1-7 from very poor to excellent. Raw score (RS) is an average of all items in each area. Standardized score is in the range of 0-100 by formula SS=[1-(RS-1)/n] x100 (function) or SS=[（RS-1）/n]x100 (symptom or overall health) respectively. A high scale score represents a higher/healthy response level.

Time to deterioration was defined as a decrease from baseline of 10 points or more on the EORTC QLQ-C30 maintained for two consecutive assessments.
Time from the date of enrollment, up to 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing YouAn Hospital

Collaborators

Beijing Gene Key Life Technology Co., Ltd.

Investigators

  • Principal Investigator: Jun Lu, MD., Beijing YouAn Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2023

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

August 1, 2025

Study Registration Dates

First Submitted

July 4, 2023

First Submitted That Met QC Criteria

July 24, 2023

First Posted (Actual)

July 27, 2023

Study Record Updates

Last Update Posted (Estimated)

January 15, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Beijing YouAn Ethics [2023]060

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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